M. Manning, W. H. Sawyer and coworkers have published a series of papers describing various [1-.beta.-mercapto-.beta.,.beta.-cyclopentamethylenepropionic acid), 4-valine]-arginine-vasopressin congeners which have anti-vasopressin activity. Among these are J. Med. Chem. 25 414-419 (1982), J. Med Chem. 25 45-50 (1982), EPA No. 61,356 and U.S. Pat. No. 4,367,225.
All of the Manning compounds have a tripeptide chain attached at unit 6 and are, of course, nonapeptides. The present compounds are distinguished over these by being octapeptides, having a dipeptide tail at unit 6 and by having potent vasopressin antagonist activity.
The potent biological activity of the compounds of the present invention is unexpected in view of the fact that de-glycinamide.sup.9 -vasopressin and de-lysine.sup.8 -glycinamide.sup.9 -vasopressin [T. Barth et al., Collection Czechoslov. Chem. Commun. 39, 506 (1974)] as well as deGly.sup.9 -oxytocin [B. Berde et al., Handb. Exp. Pharm. 23 860 (1968)] retain little of the activity of their respective parent compounds. It should be noted that "de" is used above to indicate the lack of the cited unit of the peptide, LVP or oxytocin, as in the cited publications. Hereafter, the term "des" is used for this purpose as is more common.
In the description herein and in the claims, the nomenclature common in the art of peptide and vasopressin chemistry is used. When no configuration is noted, the amino acid unit is in the L, or naturally occuring, form.